The present invention relates to organic polymer particles that can chemically bond to biological-related substances, including proteins such as an antibody or an antigen, by utilizing a carboxyl group, and can exhibit high detection sensitivity, and to a process for producing the same.
Organic polymer particles and magnetic particles are used as a reaction solid phase of a diagnostic agent using an antigen-antibody reaction in order to detect substances to be examined such as infections, cancer markers, and hormones, for example. In such a diagnostic agent, a probe (primary probe) for inspecting an antibody or an antigen is immobilized on the particles. A substance to be inspected in a sample reacts with a second inspection probe after having been trapped on the particles via the primary probe. The second inspection probe (secondary probe) is labeled with a fluorescent substance or an enzyme, whereby the target substance is detected by fluorescence or by an enzyme reaction.
In recent years, due to a demand for an increase in the inspection sensitivity for the early detection of diseases, an increase in sensitivity of a diagnostic agent has been an important subject. In order to increase sensitivity of diagnostic agents using magnetic particles, a method of using enzyme coloring as a detecting means is being replaced by a method of using fluorescence or chemiluminescence, both of which ensure higher sensitivity.
Development of these detection techniques are said to have reached a level in which a one molecule-substance for inspection can be theoretically detected. In practice, however, sensitivity is still insufficient. The incapability of maintaining the activity of the primary probe after bonding due to change in the conformation of the protein, which is the primary probe bonded to the particles, can be given as a reason for this.
Generally, as methods for maintaining the activity of such a primary probe, a method of causing a polyhydric alcohol to be present when the primary probe is bonded, and a method of bonding the primary probe via a hybrid protein bonded to the particles are disclosed (JP-A-9-304386 and WO 97/35964). However, the activity of the primary probe is insufficient when the primary probe is bonded by the method of causing a polyhydric alcohol to be present together. The method of using a hybrid protein involves a complicated and high-cost production process.